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Senile plaques and cerebral amyloid angiopathy in Alzheimer's disease (AD) patients not only consist of the amyloid-β protein (Aβ), but also contain many different Aβ-associated factors, such as heparan sulfate proteoglycans, apolipoproteins, and complement factors. These factors may all influence Aβ deposition, aggregation, and clearance and therefore seem important in the development of human Aβ deposits. To study AD pathology and test new therapeutic agents, many different mouse models have been created. By transgenic expression of the amyloid-β protein precursor, frequently in combination with other transgenes, these animals develop Aβ deposits that morphologically resemble their human counterparts. Whether this resemblance also applies to the presence of Aβ-associated factors is largely unclear. In this review, the co-deposition of factors known to associate with human Aβ deposits is summarized for several different AD mouse models. [ABSTRACT FROM AUTHOR]

Abstract: Glycosaminoglycans (GAGs), in particular as part of heparan sulfate proteoglycans, are associated with cerebral amyloid angiopathy (CAA). Similarly, GAGs are also associated with the severe CAA found in patients suffering from hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), where the amyloid β (Aβ) peptide contains the Dutch mutation (DAβ1-40). This suggests a role for GAGs in vascular Aβ aggregation. It was the aim of this study to investigate the effect of different GAGs (heparin, chondroitin sulfate, heparan sulfate), the macromolecule dextran sulfate and, using desulfated heparins, the role of GAG sulfate moieties on the in vitro aggregation of CAA-associated DAβ1-40 and on DAβ1-40-induced toxicity of cultured cerebrovascular cells. We also aimed to study the in vivo distribution of various sulfated heparan sulfate GAG epitopes in CAA. Of all GAGs tested, heparin was the strongest inducer of aggregation of DAβ1-40 in the different aggregation assays, with both heparin and heparan sulfate reducing Aβ-induced cellular toxicity. Furthermore, (partial) removal of the sulfate moieties of heparin partially abolished the effects of heparin on aggregation and cellular toxicity, suggesting an essential role for the sulfate moieties in heparin. Finally, we demonstrated the in vivo association of sulfated heparan sulfate (HS) GAGs with CAA. We conclude that sulfate moieties within GAGs, like heparin and HS, have an important role in Aβ aggregation in CAA and in Aβ-mediated toxicity of cerebrovascular cells. [Copyright &y& Elsevier]